Maintenance of the transformed phenotype in DNA and RNA tumor virus transformed cells and in cultured human tumors will be investigated with the goal of identifying cellular or viral factors responsible for driving cells through the cell cycle. The ability to form highly multinucleated cells in cytochalasin B (CB) medium, uncontrolled nuclear division (UND) will be analyzed in SV40 tsA and viable deletion mutant transformed cells. The ability to continue DNA synthesis at high saturation density and in the presence of caffeine will be studied in both DNA and RNA virus transformed cells and in cultured human tumors. The possible existence of alternate G1 yields S pathways in transformed cells will be investigated in tumor cells and DNA virus transformed cells temperature sensitive for maintenance of the transformed phenotype. UND and other phenotypes of transformation will be monitored in somatic cell hybrids and cybrids of normal x transformed and transformed x transformed cells with the goal of establishing a chromosomal and/or cytoplasmic basis for UND. The second part of the program proposes to investigate the role of papovavirus defective interfering particles (DI's) in initiation of transformation and their role in viral persistence and latency. Can DI's prevent cell killing by standard papovavirus in permissive cells and allow for transformation or latent infections? We will investigate the possibility that neural or other cells are unique in their ability to produce papovavirus defectives when infected at low multiplicities. Finally we will determine if pretreatment of permissive cells with mutagens like mitomycin C can potentiate the generation and amplification of papovavirus defectives.